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长效血友病A药物AFSTYLA（Antihemophilic Factor (Recombinant)）首个获FDA批准治疗A型血友病单链凝血因子的药物
批准日期：2016年5月31日 公司：杰特贝林(CSL Behring)
AFSTYLA®Antihemophilic因子（重组），单链
静脉注射，粉和注射用溶剂
最初美国批准：2016年
作用机理
AFSTYLA是一种重组蛋白替换所需的有效止血缺少凝血因子VIII。 AFSTYLA是单个多肽链带有截断B域，其允许共价桥的因子VIII重和轻链连接。 AFSTYLA已经证明的VWF相对于全长rFVIII.1 VWF具有更高的亲和力稳定的因子VIII和从降解保护它。激活AFSTYLA具有氨基酸序列相同的内源性FVIIIa。
适应症和用法
AFSTYLA，抗血友病因子（重组），单链，是一个重组的，在成人和儿童血友病A（先天性因子VIII缺乏）的指示抗血友病因子：
按需治疗和出血事件的控制，
常规预防减少出血发作的频率，
出血的围手术期处理。
使用限制
AFSTYLA没有为血管性血友病的治疗表示。
用法用量
仅适用于重建后静脉使用。
AFSTYLA的每个小瓶都标有在国际单位（IU或单位）的重组因子VIII的量。每公斤体重的一个单位将提高2IU/dL的因子VIII的水平。
在美国临床实验室常规使用 - 血浆因子VIII的水平可以使用一个生色测定法或一阶段凝血测定来监测。如果使用一期凝集测定，由2的换算系数相乘的结果，以确定病人的因子VIII活性水平。
计算所需剂量：
剂量（IU）=体重（公斤）×所需的因子VIII上升（IU/dl或正常％）×0.5（IU/公斤IU/分升）
常规预防：
成人和青少年（≥12岁）：
建议开始治疗方案是每给药每周2至3次AFSTYLA千克20至50 IU。
儿童（<12岁）：
建议开始治疗方案是每给药每周2至3次AFSTYLA千克30至50 IU。更频繁或更高剂量的儿童可能需要<12岁的占这一年龄组越高间隙。
该方案可根据患者的反应进行调整。
围手术期管理：
确保适当的因子VIII活动水平，实现和维护。
剂型和规格
AFSTYLA可作为在含有标称250,500，1000，2000，或3000国际单位（IU）单次使用的小瓶供给的白色或微黄色冻干粉末。
禁忌症
别在谁曾威胁生命的过敏性反应，包括过敏反应到AFSTYLA或其赋形剂，或仓鼠蛋白质的患者不能使用。
警告和注意事项
超敏反应，包括过敏性反应，是可能的。如果出现症状，请立即停止AFSTYLA和管理适当的治疗。
可发生的因子VIII的发展中和抗体（抑制剂）。如果预期血浆因子VIII活性水平没有达到，或者如果出血不与适当的剂量控制，执行该测量的因子VIII的抑制剂浓度的测定。
如果使用一期凝集测定，由2的换算系数相乘的结果，以确定病人的因子VIII活性水平。
不良反应
在临床试验报告的最常见的不良反应（>受试者0.5％）为头晕和过敏。
特殊人群中使用
小儿：
电气间隙（基于每公斤体重）是儿童患者0至<12岁的高。可能需要更高和/或更频繁的给药。
包装规格/储存与处理
附送
AFSTYLA在含在标记的因子VIII活性的量的单次使用的小瓶冻干粉末的试剂盒提供的，在国际单位（IU）表示。在国际单位（IU）实际因子VIII活动的AFSTYLA包装箱和瓶标签说明。
AFSTYLA包装用无菌注射用水，USP（2.5毫升为250，500或1000 IU的重组或5毫升为2000或3000 IU AFSTYLA重构），一个推出Mix2Vial滤波器输送装置，和一个无菌酒精棉签。组件没有由天然橡胶胶乳中。
250IU 69911-474-02
500IU 69911-475-02
1000IU 69911-476-02
2000IU 69911-477-02
3000IU 69911-478-02
储存和处理
AFSTYLA在原包装，以保护AFSTYLA小瓶避光。
AFSTYLA粉末状在2℃〜8°C（36°F至46°F）。不要冷冻，以免稀释液小瓶损坏。
AFSTYLA可以在室温下储存，以不超过25℃（77°F）时，为达到3个月的单个周期，印在包装箱和小瓶标签在有效期限内。
记录室温在未开封的产品纸箱的起始日期。一旦在室温下储存，不产品返回到冰箱。然后保质贮存后到期在室温下3个月，或在产物小瓶的截止日期，以较早者为准之后。
在小瓶指示的有效期后，不要使用AFSTYLA。
冲调出来的产品（混合与稀释液干品后）可以储存在2℃〜8°C（36°F至46°F），或在常温下不超过25°C（77°F），用于长达4小时。
避免阳光直射。
重构后，如果产品未在4小时内使用时，它必须被丢弃。
如果重组方案是浑浊或有颗粒物质不要使用AFSTYLA。
丢弃任何未使用的AFSTYLA。
完整资料附件：https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=51f19873-a63f-4229-9477-5da4ecf31cde
Afstyla(Antihemophilic Factor Recombinant Intravenous Injection)
U.S. Food and Drug Administration (FDA) has approved Afstyla [Antihemophilic Factor (Recombinant), Single Chain], its novel long-lasting recombinant factor VIII single-chain therapy for adults and children with hemophilia A. Afstyla is the first and only single-chain product for hemophilia A that is specifically designed for long-lasting protection from bleeds with two to three times weekly dosing. In clinical trials, patients undergoing prophylaxis with Afstyla experienced a median annualized spontaneous bleeding rate (AsBR) of 0.00. Once activated, Afstyla is identical to natural factor VIII. Clinical trials of Afstyla demonstrated a strong safety profile with no inhibitors observed.
Important Safety Information for AFSTYLA
AFSTYLA®, Antihemophilic Factor (Recombinant), Single Chain, is contraindicated in patients who have had life-threatening hypersensitivity reactions to AFSTYLA or its excipients, or to hamster proteins.
AFSTYLA is for intravenous use only. AFSTYLA can be self-administered or administered by a caregiver with training and approval from a healthcare provider or hemophilia treatment center. Higher and/or more frequent dosing may be needed for patients under 12 years of age.
Hypersensitivity reactions, including anaphylaxis, are possible. Advise patients to immediately report symptoms of a hypersensitivity reaction. If symptoms occur, discontinue AFSTYLA and administer appropriate treatment.
Development of Factor VIII (FVIII) neutralizing antibodies (inhibitors) can occur. If expected FVIII activity levels are not attained or bleeding is not controlled with appropriate dose, perform an assay to measure FVIII inhibitor concentration.
Monitor plasma FVIII activity using a chromogenic assay or one-stage clotting assay. If one-stage clotting assay is used, multiply result by a conversion factor of 2 to determine FVIII activity level.
The most common adverse reactions reported in clinical trials (>0.5%) were dizziness and hypersensitivity.
Indications for AFSTYLA
AFSTYLA is indicated in adults and children with hemophilia A (congenital Factor VIII deficiency) for:
•On-demand treatment and control of bleeding episodes
•Routine prophylaxis to reduce frequency of bleeding episodes
•Perioperative management of bleeding
AFSTYLA is not indicated for the treatment of von Willebrand disease.
Please see full prescribing information for AFSTYLA.
Important Safety Information for HELIXATE FS
HELIXATE® FS is contraindicated in patients who have life-threatening hypersensitivity reactions, including anaphylaxis to mouse or hamster protein or other constituents of the product.
Hypersensitivity reactions, including anaphylaxis have been reported with HELIXATE FS. Reported symptoms included facial swelling, flushing, hives, decrease in blood pressure, nausea, rash, restlessness, shortness of breath, tachycardia, tightness of the chest, tingling, urticaria, and vomiting. Discontinue HELIXATE FS if symptoms occur and seek immediate emergency treatment.
Neutralizing antibodies (inhibitors) have been reported following administration of HELIXATE FS predominately in previously untreated patients. Carefully monitor patients for the development of Factor VIII inhibitors, using appropriate clinical observations and laboratory tests. If expected plasma Factor VIII activity levels are not attained, or if bleeding is not controlled with an expected dose, perform an assay that measures Factor VIII inhibitor concentration.
Hemophilic patients with cardiovascular risk factors or diseases may be at the same risk to develop cardiovascular events as non-hemophilic patients when clotting has been normalized by treatment with Factor VIII.
Serious adverse reactions seen with HELIXATE FS are systemic hypersensitivity reactions including bronchospastic reactions and/or hypotension and anaphylaxis, and the development of high-titer inhibitors necessitating alternative treatments to Factor VIII.
The most common adverse reactions (≥4%) observed in clinical trials were inhibitor formation in previously untreated and minimally treated patients, skin-related hypersensitivity reactions, infusion site reactions, and central venous access device (CVAD) associated infections.
Indications for HELIXATE FS
HELIXATE FS, Antihemophilic Factor (Recombinant), is a recombinant Factor VIII indicated for:
•Control and prevention of bleeding episodes in adults and children with hemophilia A
•Surgical prophylaxis in adults and children with hemophilia A
•Routine prophylactic treatment to prevent or reduce the frequency of bleeding episodes in children with hemophilia A and to reduce the risk of joint damage in children without pre-existing joint damage
•Routine prophylactic treatment to prevent or reduce the frequency of bleeding episodes in adults with hemophilia A
HELIXATE FS is not indicated for the treatment of von Willebrand disease.
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